Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Semczuk, Andrzej; Ignatov, Atanas; Obrzut, Bogdan; Reventós, Jaume; Rechberger, Tomasz

doi:10.1159/000363574

Cited by 7 publications

(4 citation statements)

References 104 publications

(170 reference statements)

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“…Genetic alterations of TP53 have been thoroughly investigated in human cancer [13]. It is known that TP53 mutations occur during CS tumourigenesis, causing the gene to lose its tumour suppressive function, indicating its role as an early pathogenetic driver [8, 14]. The distribution pattern of TP53 mutations found by us was in line with that found in previous studies [7].…”

Section: Discussionsupporting

confidence: 87%

Molecular characterization of carcinosarcomas arising in the uterus and ovaries

et al. 2019

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Gynaecological carcinosarcomas are rare biphasic tumours which are highly aggressive. We performed molecular investigations on a series of such tumours arising in the uterus ( n = 16) and ovaries ( n = 10) to gain more information on their mutational landscapes and the expression status of the genes HMGA1/2 , FHIT , LIN28A , and MTA1 , the pseudogenes HMGA1P6 and HMGA1P7 , and the miRNAs known to influence expression of the above-mentioned genes. In uterine carcinosarcomas (UCS), we identified mutations in KRAS , PIK3CA , and TP53 with a frequency of 6%, 31%, and 75%, respectively, whereas in ovarian carcinosarcomas (OCS), TP53 was the only mutated gene found (30%). An inverse correlation was observed between overexpression of HMGA1/2 , LIN28A , and MTA1 and downregulation of miRNAs such as let-7a, let-7d, miR26a, miR16, miR214, and miR30c in both UCS and OCS. HMGA2 was expressed in its full length in 14 UCS and 9 OCS; in the remaining tumours, it was expressed in its truncated form. Because FHIT was normally expressed while miR30c was downregulated, not both downregulated as is the case in several other carcinomas, alterations of the epithelial-mesenchymal transition through an as yet unknown mechanism seems to be a feature of carcinosarcomas.

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Section: Discussionsupporting

confidence: 87%

Molecular characterization of carcinosarcomas arising in the uterus and ovaries

et al. 2019

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“…MiR‐125b was reported to act as an oncogene in glioblastoma cells, and inhibit cell apoptosis by p53 and p38MAPK‐independent pathways. Moreover, the alterations of p53 pathway have been shown to be associated with uterine carcinosarcomas as well (Semczuk et al, ). Additionally, has‐miR‐133a also activates the p53 pathway and acts as a tumor suppressor in colorectal cancer (Prabhu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis and MicroRNA Expression Profiling Identified Seven miRNAs Associated With Progression of Oral Squamous Cell Carcinoma

Yan

Luo

Zhang

et al. 2017

Journal Cellular Physiology

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MicroRNAs have been used as diagnostic and prognostic biomarkers for many cancers including oral squamous cell carcinoma (OSCC). Several studies have been shown that microRNA (miRNA) play important roles during the progression of OSCC. However, the results vary largely in different studies due to different platforms and sample sizes. In this study, we systematically evaluated a large scale of miRNA profiles from current qualified OSCC samples, and further investigated the functions of genes regulated by these key miRNAs as well as the signaling pathways through which these miRNA effect carcinogenesis. Seven key miRNAs were identified, and of which three were significantly upregulated, including hsa-miR-21, hsa-miR-31, hsa-miR-338, and four were downregulated, namely hsa-miR-125b, hsa-miR-133a, hsa-miR-133b, and hsa-miR-139. The function enrichment analysis revealed that target genes of upregulated miRNAs were associated with cellular protein metabolic process, macromolecule metabolic process, and TGF-beta pathway, while the targets of downregulated were enriched in negative regulation of macromolecule biosynthetic process and gene expression, and p53, long-term potentiation and adherens junction pathways. Transcription factor analysis revealed that there were 67 (51.1%) transcription factors influenced by both up and downregulated miRNAs. In summary, seven key miRNAs were found to play essential role in progression of OSCC, as well as the target genes and transcription factors of these miRNAs. The potential functions of these target genes identified in our study may be profitable to diagnosis and prognostic prediction of OSCC as biomarkers. J. Cell. Physiol. 232: 2178-2185, 2017. © 2016 Wiley Periodicals, Inc.

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“…Based on the fact that their histogenesis remains a matter of controversy, the assessment of cell proliferation is an innovative and interesting task. The present study is an extension of our broad scientific interest in investigating the impact of various IHC/genetic alterations on the development and progression of UCs and their corresponding metastases (26,(39)(40)(41)(42)(43). In the present study, an enhanced proliferative expression pattern of all markers was demonstrated in the carcinomatous component of UC, as compared with the sarcomatous one.…”

Section: Discussionmentioning

confidence: 99%

Inter‑component immunohistochemical assessment of proliferative markers in uterine carcinosarcoma

Pyra¹,

Adamiak‐Godlewska

Lewkowicz

et al. 2022

Oncol Lett

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In the scientific literature, a selected number of reports have investigated the impact of proliferative activity on the development and progression of uterine carcinosarcomas (UC). The aim of the present retrospective study was to compare the immunohistochemical proliferation markers [Ki67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 3 (MCM3), and topoisomerase IIα (topoIIα)] assessment in both components of UC. A total of 30 paraffin-embedded slides of UCs, obtained from patients who underwent surgery between January 1, 2006, and December 31, 2020, were analyzed. Medical records and clinicopathological data of patients were reviewed. Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki67, PCNA, MCM3 and topoIIα. Ki67-positive nuclear immunoreactivity was reported in 20 (67%) and 16 (53%) UC carcinomatous and sarcomatous components, respectively. In the epithelial component, Ki67 positive staining was related to the International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.025), and histological grade (G1 vs. G2/G3, P=0.031). Nuclear PCNA reactivity was observed in 18 (60%) and 16 (53%) carcinomatous and sarcomatous components, respectively. Notably, all four cases with omental metastases were PCNA-positive, and a relationship between staining pattern and the existence of metastases was of significant value (P= 0.018). MCM3-positive nuclear staining was found nearly twice as high in the carcinomatous (n=19; 63%), compared with the sarcomatous (n=11; 37%) component, respectively, and MCM3 expression in the epithelial component was related to clinical stage (P=0.030), and the existence of omental metastasis (P=0.012). In addition, out of the 30 UCs, 17 (57%) and 13 (43%) showed topoIIα positivity in the carcinomatous and sarcomatous UC components, respectively. A significant relationship between protein immunoreactivity and FIGO stage (P=0.049), and omental metastasis (P=0.026) was revealed to exist. However, no significant differences between expression of proliferation markers and clinicopathological features in the sarcomatous UC component were identified. Finally, a significant correlation between each protein immunohistochemical staining was demonstrated, particularly in the sarcomatous UC component. Collectively, a combined analysis of Ki67, PCNA, MCM3, and topoIIα may provide more detailed information of cell-cycle alterations determining the heterogeneity of uterine carcinosarcomas.

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Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Cited by 7 publications

References 104 publications

Molecular characterization of carcinosarcomas arising in the uterus and ovaries

Molecular characterization of carcinosarcomas arising in the uterus and ovaries

Integrated Analysis and MicroRNA Expression Profiling Identified Seven miRNAs Associated With Progression of Oral Squamous Cell Carcinoma

Inter‑component immunohistochemical assessment of proliferative markers in uterine carcinosarcoma

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